IL-6 is an important physiologically active factor which is involved not only in the immune system but also in the proliferation and differentiation of hematopoietic progenitor cells, induction of acutephase proteins and differentiation of nerve cells. The biological activities of said IL-6 may be classified roughly into three types, namely (1) induction of cell differentiation or induction of the expression of certain genes, (2) induction of cell proliferation and (3) inhibition of cell proliferation. It has been shown that IL-6 produce quite different biological activities against different targent cells [Hirano, T. and Kishimoto, T., Jikken Igaku, 7 (1), 11-12 (1989)].
On the other hand, it is known that IL-6 is produced to an abnormal extent in patients with certain autoimmune diseases or cancer, among others [Kishimoto, T. and Hirano, T.: Molecular regulation of B lymphocyte response, Ann. Rev. Immunol., 6, 485-512 (1988)].
Analysis of the genes of cells abnormally producing IL-6 in patients with diseases accompanied by abnormal IL-6 production has revealed that the gene coding for IL-6 itself has not undergone any gene mutation or any other changes in its structure. This suggests that the abnormal IL-6 production mentioned above might be induced by occurrence of an abnormality in a nuclear factor which controls the transcription of the IL-6 gene.
Meanwhile it is known that the production of IL-6 is induced by stimulation from interleukin-1 (IL-1) [Kishimoto, T. and Hirano, T.: Molecular regulation of B lymphocyte response, Ann. Rev. Immunol., 6, 485-512 (1988)].
The present inventors made intensive investigations in the belief that a nuclear factor capable of directing acting on the IL-1-induced IL-6 gene expression must be found in glioblastoma cells (tumor cells derived from cerebral glia cells) [SK-MG4; Yasukawa, K, et al., EMBO Journal, 6, 2939-2945 (1987)]and, as a result, found that a region having homology to c-fos SRE [Treisman, R., Cell, 42, 889-902 (1985)]occurs in the 5' upstream region of the IL-6 gene and that there is a nuclear factor capable of sequence-specifically binding to the 14 bp palidrome structure SEQ ID NO:2 occurring in said region homologous to c-fos SRE. Said nuclear factor was first named NF-IL6 (Akira, S. et al., Abstracts of Papers presented at the Annual Meeting of the Japanese Society for Immunology for 1988, page 281). The name of said factor has been changed to C/EBP2.
It is an object of the invention to isolate the gene coding for the nuclear factor (i.e. C/EBP2) capable of sequence-specifically binding to the above-mentioned base sequence SEQ ID NO:2, determine the base sequence of said gene, and produce C/EBP2 by using said gene and the recombinant DNA technology.